由Ant2缺乏驱动的代谢重编程增加了小鼠的T细胞功能和抗瘤免疫力
Omri Yosef1, Leonor Cohen-Daniel1, Oded Shamriz1
1The Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Nature communications
|May 9, 2025
概括
缺乏ADP/ATP转位酶-2 (Ant2) 的小鼠表现出增强的T细胞激活和功能. 向ANT可能通过调节T细胞代谢来改善癌症免疫疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 线粒体生物学 线粒体生物学
背景情况:
- T细胞激活需要显著的NAD+生产,往往超过氧化酸化 (OXPHOS) 能力.
- ADP/ATP转位酶-2 (Ant2) 促进线粒体-细胞质ADP/ATP交换,这对细胞能量恒温至关重要.
研究的目的:
- 研究Ant2在激活期间T细胞代谢适应中的作用.
- 探索针对T细胞介导免疫中的Ant2的治疗潜力.
主要方法:
- 产生T细胞特异性Ant2淘汰 (Ant2-/-) 鼠.
- 野生类型和Ant2-/- T细胞的代谢分析和功能测定.
- 在野生型T细胞中药理上抑制ANT,并在癌症模型中进行评估.
主要成果:
- Ant2缺乏限制了OXPHOS,限制了NAD+再生,但增强了T细胞激活,增殖和效应器功能.
- Ant2-/- T 细胞表现出活性化代谢表型,具有增强的线粒体生成和代谢.
- 在野生型T细胞中药理上的ANTT抑制模仿了Ant2-/-表型,并提高了采用T细胞治疗的疗效.
结论:
- 缺乏Ant2的T细胞绕过了典型的代谢重编程,导致功能增强.
- 向ANTT为免疫调节和改善癌症免疫治疗提供了一个潜在的战略.
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